212 B.M. Buddle et al.
European Union. Recently, it was shown that
infection of goats with a low dose of M. caprae
(10^3 CFU) via the endobronchial route produced
lesions in all infected animals at 14 weeks after
infection, showing pathology reflecting the nat-
ural disease of caseous necrotic and cavitary
lesions in the lungs (Pérez de Val et al., 2011). In
contrast, aerosol infection of goats with a simi-
lar dose of M. bovis produced small pulmonary
lesions (Gonzalez-Juarrero et al., 2013). This dif-
ference in pathology may have arisen from dif-
ferences in routes of infection as in a subsequent
study where groups of goats were challenged
transthoracically with either M. bovis or M. cap-
rae, the total lesion scores and culture results
were higher for the M. bovis-challenged goats
(Bezos et al., 2015). To determine protective effi-
cacy of vaccines, gross and microscopic lesions
have been assessed by qualitative and quantita-
tive analyses, together with mycobacterial cul-
ture from lung-associated lymph nodes. The
precise determination of the total lung lesion
burden related to total lung volume has been
achieved using multi-detector computed tomog-
raphy (Pérez de Val et al., 2011).
BCG Danish vaccine administered subcuta-
neously at a dose of 5 × 105 CFU was shown to be
safe and no shedding of BCG was detected in the
faeces of vaccinated kids or in the milk of vacci-
nated, lactating goats (Pérez de Val et al., 2016).
BCG was isolated from a lymph node draining the
site of vaccination from one kid at 8-weeks post-
vaccination, but not from any goats at 24-weeks
post-vaccination. A single dose of BCG vaccine
administered subcutaneously to goats was
shown to significantly induce protection against
challenge with M. caprae, with reductions in pul-
monary pathology and bacterial load. The test-
ing in goats of a heterologous prime/boost with
BCG followed by virus- vectored vaccines, Ad5-
Ag85A or Ad5-TBF, have provided encouraging
results with significant protection against endo-
bronchial M. caprae challenge compared to those
receiving BCG vaccine alone or the non-
vaccinates (Pérez de Val et al., 2012, 2013). Vac-
cination with BCG or BCG plus Ad5-Ag85A
appeared to prevent haematogenous dissemina-
tion of mycobacteria with extra-thoracic TB
lesions only found in non-vaccinated goats (Pérez
de Val et al., 2012). Furthermore, use of myco-
bacterial DIVA reagents, ESAT-6 and CFP10, in
the IFN-γ tests were able to differentiate
TB-infected from BCG-vaccinated goats. In vac-
cinated goats, cultured IFN-γ ELISPOT responses
against Ag85A correlated significantly with pro-
tection (Pérez de Val et al., 2013), concurring
with results in cattle that measurement of spe-
cific IFN-γ- producing memory cells could be a
predictor of TB vaccine efficacy.
Vaccination has been seen as a valuable
long-term control prospect, reducing the TB
prevalence prior to starting a test-and-slaughter
eradication programme which would reduce
economic costs for producers and the public sec-
tor. In addition, the goat model has considerable
potential for testing candidate human TB vac-
cines and has a number of advantages including
similar TB pathology such as the development of
lung cavitary lesions and a lower cost compared
to that for the model in cattle.14.4 Vaccination of DeerVaccination studies of deer have been under-
taken to assess whether vaccination could be an
effective method of protecting farmed deer from
TB and to develop a system for vaccinating feral
deer to prevent re-infection back into cattle
herds. TB in wild or farmed deer is predomi-
nantly caused by M. bovis, and commonly, tuber-
culous lesions are described as liquefied or
abscess-like in contrast to the caseous nature of
the lesions seen in cattle and goats (Beatson,
1985; Fitzgerald and Kaneene, 2013). The dis-
tribution of the tuberculous lesions also differs
from those in cattle with the retropharyngeal
lymph nodes being the most common site for
lesions in deer, followed by lesions in the lungs
and associated lymph nodes as well as in the
mesenteric lymph nodes (Martín-Hernando
et al., 2010). The primary lesion complex in deer
appears to be tonsils and retropharyngeal lymph
nodes, suggesting an oral or aerosol route of
infection. To reproduce the typical pathology
seen in natural infected deer, low doses of
M. bovis (10^2 CFU) have been instilled into the
tonsillar crypts with lesions developing in the
tonsils and retropharyngeal lymph nodes ( Griffin
et al., 1995; Palmer et al., 2002b).
Studies of BCG vaccine in deer have shown
that a single dose of BCG administered subcuta-
neously to 3-month-old deer could reduce